Reactome | YWHAE dimer binds phosphorylated DENND1 proteins

YWHAE dimer binds phosphorylated DENND1 proteins

Stable Identifier

R-HSA-8933452

Type

Reaction [binding]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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YWHAE dimer binds phosphorylated DENND1 proteins

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RAB35 GEFs DENND1A and DENND1B are phosphorylated by AKT in response to insulin signaling at at least 2 sites in the C-terminal region. This phosphorylation relieves an autoinhibitory conformation of the GEF that sterically blocks the N-terminal DENN domain, obstructing RAB35 binding and full GEF activity. Subsequent to AKT-dependent phosphorylation, DENN1D proteins are bound by a 14-3-3 dimer, which is thought to stabilize the open conformation of the GEF, promoting full GEF activity and RAB35 binding (Kulasekaran et al, 2015). Active RAB35 contributes to GLUT4 translocation to the plamsa membrane in response to insulin signaling, among other cellular roles (Kulasekaran et al, 2015; Davey et al, 2012; Humphrey et al, 2013).

Literature References

PubMed ID	Title	Journal	Year
26055712	Phosphorylation-dependent Regulation of Connecdenn/DENND1 Guanine Nucleotide Exchange Factors Nossova, N, Kulasekaran, G, Lund, I, Cremer, C, Marat, AL, Ioannou, MS, McPherson, PS	J. Biol. Chem.	2015
22762500	TBC1D13 is a RAB35 specific GAP that plays an important role in GLUT4 trafficking in adipocytes Stöckli, J, James, DE, Davey, JR, Lambright, DG, Mishra, AK, Junutula, JR, Humphrey, SJ	Traffic	2012
23684622	Dynamic adipocyte phosphoproteome reveals that Akt directly regulates mTORC2 James, DE, Yang, G, Stöckli, J, Fazakerley, DJ, Yang, P, Yang, JY, Humphrey, SJ	Cell Metab.	2013